title: Sodium/calcium exchanger is upregulated by sulfide signaling, forms complex with the β1 and β3 but not β2 adrenergic receptors, and induces apoptosis.
abstract: Hydrogen sulfide (H2S) as a novel gasotransmitter regulates variety of processes, including calcium transport systems. Sodium calcium exchanger (NCX) is one of the key players in a regulation calcium homeostasis. Thus, the aims of our work were to determine effect of sulfide signaling on the NCX type 1 (NCX1) expression and function in HeLa cells, to investigate the relationship of β-adrenergic receptors with the NCX1 in the presence and/or absence of H2S, and to determine physiological importance of this potential communication. As a H2S donor, we used morpholin-4-ium-4-methoxyphenyl(morpholino) phosphinodithioate-GYY4137. We observed increased levels of the NCX1 mRNA, protein, and activity after 24 h of GYY4137 treatment. This increase was accompanied by elevated cAMP due to the GYY4137 treatment, which was completely abolished, when NCX1 was silenced. Increased cAMP levels would point to upregulation of β-adrenergic receptors. Indeed, GYY4137 increased expression of β1 and β3 (but not β2) adrenergic receptors. These receptors co-precipitated, co-localized with the NCX1, and induced apoptosis in the presence of H2S. Our results suggest that sulfide signaling plays a role in regulation of the NCX1, β1 and β3 adrenergic receptors, their co-localization, and stimulation of apoptosis, which might be of a potential importance in cancer treatment.
authors.affiliation: Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences (SAS), Vlarska 5, 833 34, Bratislava, Slovak Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Markova
authors.forename: Sona
authors.initials: S
authors.lastname: Hudecova
authors.forename: Andrea
authors.initials: A
authors.lastname: Soltysova
authors.forename: Marta
authors.initials: M
authors.lastname: Sirova
authors.forename: Lucia
authors.initials: L
authors.lastname: Csaderova
authors.forename: Lubomira
authors.initials: L
authors.lastname: Lencesova
authors.forename: Karol
authors.initials: K
authors.lastname: Ondrias
authors.forename: Olga
authors.initials: O
authors.lastname: Krizanova
mesh_terms: D017209:Apoptosis; D000242:Cyclic AMP / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D000242:Cyclic AMP; D006862:Hydrogen Sulfide